From the Guidelines
The primary treatment for metastatic Gastrointestinal Stromal Tumor (GIST) is imatinib at a dose of 400 mg daily, which should be continued indefinitely until disease progression or intolerable toxicity occurs. This recommendation is based on the most recent and highest quality study available, which suggests that imatinib is the standard upfront treatment for locally advanced inoperable and metastatic disease [ 1 ].
Treatment Options
- Imatinib is the first-line treatment, with a standard dose of 400 mg daily [ 1 ].
- For patients with KIT exon 9 mutations, a higher dose of 800 mg daily may be more effective [ 1 ].
- If progression occurs on imatinib, second-line therapy with sunitinib at 50 mg daily for 4 weeks on, 2 weeks off is recommended [ 1 ].
- Third-line treatment involves regorafenib at 160 mg daily for 3 weeks on, 1 week off [ 1 ].
- For patients with specific mutations like PDGFRA D842V, avapritinib at a recommended dose may be more effective [ 1 ].
Additional Considerations
- Surgical resection of metastatic disease may be considered in selected patients with good response to tyrosine kinase inhibitors [ 1 ].
- Interventional techniques like radiosurgery or radiofrequency ablation may be options in selected cases [ 1 ].
- Treatment schedule and dose should be adapted to the patient's tolerability, and regular monitoring with CT scans every 3-6 months is essential to assess response [ 1 ].
Quality of Life and Morbidity
- The goal of treatment is to improve overall survival and quality of life, while minimizing morbidity and toxicity [ 1 ].
- Dose reductions or treatment interruptions may be necessary to manage intolerable toxicity, and alternative treatment options should be considered in cases of disease progression or rare intolerance to imatinib [ 1 ].
From the FDA Drug Label
- 2 Gastrointestinal Stromal Tumors STIVARGA is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.
The treatment option for metastatic Gastrointestinal Stromal Tumor (GIST) is regorafenib (STIVARGA), for patients who have been previously treated with imatinib mesylate and sunitinib malate 2.
From the Research
Treatment Options for Metastatic GIST
- The standard first-line treatment for metastatic Gastrointestinal Stromal Tumor (GIST) is tyrosine kinase inhibitor (TKI) therapy, specifically imatinib 3, 4, 5, 6.
- High-dose imatinib (800 mg daily) may be beneficial for patients with advanced or metastatic GIST that progresses on standard-dose imatinib, particularly those with KIT exon 9 mutation 3.
- For patients who develop secondary resistance to imatinib, second-line treatment options include sunitinib and regorafenib 4, 5, 6.
- Ripretinib, a switch-control tyrosine kinase inhibitor, has been approved for fourth-line treatment in metastatic GIST 4.
- Avapritinib, a TKI, has been approved for metastatic GIST harboring the imatinib-resistant PDGFRA exon 18 mutation 4.
Surgical Management
- Cytoreductive surgery may be considered in patients with metastatic GIST who respond to imatinib, particularly if a R0/R1 resection is achieved 4, 7.
- Surgery should be considered in patients with metastatic GIST whose disease responds to imatinib, with a goal of performing R0/R1 resection 7.
- Optimal timing of surgery is unclear, but should be considered between 6 months and 2 years after starting imatinib 7.
- Patients with metastatic GIST should resume tyrosine kinase inhibitor treatment postoperatively 4, 7.
Considerations for Treatment
- Before switching to second-line treatment, consideration should be given to factors such as false progression, insufficient TKI plasma levels, and patient non-adherence 5.
- Imatinib dose escalation may be beneficial for patients with true progression 5.
- Surgery may provide a viable option for patients with stable disease or limited progression, and may prevent and/or delay the development of resistant clones by reducing tumor burden 5.